Luo Zhongling, Zhang Xu, Zeng Weiqi, Su Juan, Yang Keda, Lu Lixia, Lim Chuan Bian, Tang Wen, Wu Lisha, Zhao Shuang, Jia Xuekun, Peng Cong, Chen Xiang
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Oncotarget. 2016 Feb 9;7(6):7179-92. doi: 10.18632/oncotarget.6886.
TRAF6 plays a crucial role in the regulation of the innate and adaptive immune responses. Although studies have shown that TRAF6 has oncogenic activity, the role of TRAF6 in melanoma is unclear. Here, we report that TRAF6 is overexpressed in primary as well as metastatic melanoma tumors and melanoma cell lines. Knockdown of TRAF6 with shRNA significantly suppressed malignant phenotypes including cell proliferation, anchorage-independent cell growth and metastasis in vitro and in vivo. Notably, we demonstrated that Basigin (BSG)/CD147, a critical molecule for cancer cell invasion and metastasis, is a novel interacting partner of TRAF6. Furthermore, depletion of TRAF6 by shRNA reduced the recruitment of BSG to the plasma membrane and K63-linked ubiquitination, in turn, which impaired BSG-dependent MMP9 induction. Taken together, our findings indicate that TRAF6 is involved in regulating melanoma invasion and metastasis, suggesting that TRAF6 may be a potential target for therapy or chemo-prevention in melanoma.
TRAF6在先天性和适应性免疫反应的调节中起着关键作用。尽管研究表明TRAF6具有致癌活性，但其在黑色素瘤中的作用尚不清楚。在此，我们报告TRAF6在原发性和转移性黑色素瘤肿瘤以及黑色素瘤细胞系中均过度表达。用短发夹RNA（shRNA）敲低TRAF6可显著抑制恶性表型，包括体外和体内的细胞增殖、不依赖贴壁的细胞生长和转移。值得注意的是，我们证明了基底膜蛋白（BSG）/CD147，一种癌细胞侵袭和转移的关键分子，是TRAF6的新型相互作用伴侣。此外，shRNA介导的TRAF6缺失减少了BSG向质膜的募集以及K63连接的泛素化，进而损害了BSG依赖性基质金属蛋白酶9（MMP9）的诱导。综上所述，我们的研究结果表明TRAF6参与调节黑色素瘤的侵袭和转移，提示TRAF6可能是黑色素瘤治疗或化学预防的潜在靶点。
